Melanin is ubiquitous in living organisms across different biological kingdoms of life, making it an important, natural biomaterial. Its presence in nature from microorganisms to higher animals and plants is attributed to the many functions of melanin, including pigmentation, radical scavenging, radiation protection, and thermal regulation. Generally, melanin is classified into five typeseumelanin, pheomelanin, neuromelanin, allomelanin, and pyomelaninbased on the various chemical precursors used in their biosynthesis. Despite its long history of study, the exact chemical makeup of melanin remains unclear, and it moreover has an inherent diversity and complexity of chemical structure, likely including many functions and properties that remain to be identified. Synthetic mimics have begun to play a broader role in unraveling structure and function relationships of natural melanins. In the past decade, polydopamine, which has served as the conventional form of synthetic eumelanin, has dominated the literature on melaninbased materials, while the synthetic analogues of other melanins have received far less attention. In this perspective, we will discuss the synthesis of melanin materials with a special focus beyond polydopamine. We will emphasize efforts to elucidate biosynthetic pathways and structural characterization approaches that can be harnessed to interrogate specific structure−function relationships, including electron paramagnetic resonance (EPR) and solid-state nuclear magnetic resonance (ssNMR) spectroscopy. We believe that this timely Perspective will introduce this class of biopolymer to the broader chemistry community, where we hope to stimulate new opportunities in novel, melanin-based poly-functional synthetic materials.

Thermophysical and structural properties of two binary mixtures of ionic liquids were determined in this study using molecular dynamics simulations at 353 K. The mixtures contains common cation and different anions, combining 1-n-butyl-3-methylimidazolium [C 4 mim] + chloride [Cl] − with two other ionic liquids, namely, [C 4 mim] + methylsulfate [MeSO 4 ] − and [C 4 mim] + bis(trifluoromethanesulfonyl)imide [NTf 2 ] − . Each mixture was characterized in terms of thermodynamic quantities such as densities and excess molar volumes and transport properties specifically selfdiffusion coefficients and ionic conductivities, using seven molar compositions (0:00, 10:90, 25:75, 50:50, 75:25, 90:10, 100:0). Excess molar volumes for the two binary ionic liquid mixtures exhibited small deviations from ideality; the Cl-[MeSO 4 ] system showed negative deviation while positive deviation was observed for the Cl-[NTf 2 ] system. Structural analysis elucidated in terms of radial distribution functions, orientations of the anions around cation through angular distribution functions, and spatial distribution functions revealed that the significant changes in the ionic interactions occur within the first solvation shell of the cations and these changes are responsible for the observed nonideality. The self-diffusion coefficients of the ions were found to decrease monotonically with Cl − concentration for both the mixtures. Further, predictions of ionic conductivities using both the Nernst−Einstein formalism and Einstein relationship pointed to the presence of correlated ionic motion which was confirmed by the long ion-pair relaxation time constants especially for the anion present as a minor component.

Heterochromatin protein 1α (HP1α) is a crucial element of chromatin organization. It has been proposed that HP1α functions through liquid-liquid phase separation (LLPS), which allows it to compact chromatin into transcriptionally repressed heterochromatin regions. In vitro, HP1α can undergo phase separation upon phosphorylation of its N-terminus extension (NTE) and/or through interactions with DNA and chromatin. Here, we combine computational and experimental approaches to elucidate the molecular interactions that drive these processes. In phosphorylation-driven LLPS, HP1α can exchange intradimer hinge-NTE interactions with interdimer contacts, which also leads to a structural change from a compacted to an extended HP1α dimer conformation. This process can be enhanced by the presence of positively charged HP1α peptide ligands and disrupted by the addition of negatively charged or neutral peptides. In DNA-driven LLPS, both positively and negatively charged peptide ligands can perturb phase separation. Our findings demonstrate the importance of electrostatic interactions in HP1α LLPS where binding partners can modulate the overall charge of the droplets and screen or enhance hinge region interactions through specific and non-specific effects. Our study illuminates the complex molecular framework that can fine-tune the properties of HP1α and that can contribute to heterochromatin regulation and function.

A variety of membraneless organelles, often termed “biological condensates”, play an important role in the regulation of cellular processes such as gene transcription, translation, and protein quality control. On the basis of experimental and theoretical investigations, liquid–liquid phase separation (LLPS) has been proposed as a possible mechanism for the origin of biological condensates. LLPS requires multivalent macromolecules that template the formation of long-range, intermolecular interaction networks and results in the formation of condensates with defined composition and material properties. Multivalent interactions driving LLPS exhibit a wide range of modes from highly stereospecific to nonspecific and involve both folded and disordered regions. Multidomain proteins serve as suitable macromolecules for promoting phase separation and achieving disparate functions due to their potential for multivalent interactions and regulation. Here, we aim to highlight the influence of the domain architecture and interdomain interactions on the phase separation of multidomain protein condensates. First, the general principles underlying these interactions are illustrated on the basis of examples of multidomain proteins that are predominantly associated with nucleic acid binding and protein quality control and contain both folded and disordered regions. Next, the examples showcase how LLPS properties of folded and disordered regions can be leveraged to engineer multidomain constructs that form condensates with the desired assembly and functional properties. Finally, we highlight the need for improvements in coarse-grained computational models that can provide molecular-level insights into multidomain protein condensates in conjunction with experimental efforts.

Molecular dynamics (MD) simulations were conducted to investigate the variation of Henry’s constant of CO2 in two binary ionic liquid mixtures. One of the mixtures is formed by pairing the cation 1-n-butyl-3-methylimidazolium [C4mim]+ with chloride Cl– and methylsulfate [MeSO4]−, whereas the other binary ionic liquid mixture contains [C4mim]+ in combination with the anions Cl– and bis­(trifluoromethanesulfonyl)­imide [NTf2]−. In order to provide a microscopic understanding of the behavior of the Henry’s constant with the anion composition, MD simulations of ionic liquid mixtures with and without CO2 saturation were performed at 353 K and 10 bar. Our calculations indicate that the Henry’s constant for CO2 follows a highly nonlinear, although expected based on ideal solubility, trend with respect to the increasing concentration of Cl– in [C4mim]­Cl x [NTf2]1–x , whereas the Henry’s constant is almost independent of the anion composition in the [C4mim]­Cl x [MeSO4]1–x system. Structural analyses presented in terms of radial, spatial, and angular distribution functions point to significant structural reorganization of the anions around cations in the [C4mim]­Cl x [NTf2]1–x system. Because of the weakly coordinating ability of the [NTf2]− anion with the cation, the [NTf2]− anion is displaced from the equatorial plane of the imidazolium ring and occupies positions above and below the ring, enabling enhanced CO2–[NTf2]− association. The rearrangement also weakens the cation π–π interactions, resulting in the formation of increased local free volume aiding CO2 accommodation. On the contrary, such structural transitions are absent in the [C4mim]­Cl x [MeSO4]1–x mixture system.